Abstract
Background
Parental history of coronary artery disease (CAD) is considered an important risk factor for early atherosclerosis
Hypothesis
The onset of the inflammatory process of atherosclerosis initiates early during childhood in children with positive family history (PFH) of CAD.
Methods
We studied 55 healthy children (5–15 years), 30 (16 male) with PFH and 25 age and sex matched control subjects. Blood samples were taken to measure white blood count (WBC), glucose, total cholesterol, triglycerides (TG), high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), erythrocyte sedimentation rate (SDE), C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐a). We performed cultures on monocytes (from peripheral blood) measuring in the cell culture supernatants the proinflammatory cytokines IL‐6 and TNF‐a, by using the immunoassay ELISA method.
Results:
Higher values of body mass index (BMI), total cholesterol, LDL, cholesterol, TG, SDE, leucocytes, and CRP were calculated in children with PFH. Significantly higher values of cytokines in monocell cultures were measured in the PFH group compared to the control group (IL‐6 = 139.32 ± 80.84 pg/ml versus 14.30 ± 12.97 pg/ml, p < 0.001 and TNF‐a = 39.91 ± 11.80 pg/ml versus 8.65 ± 4.35 pg/ml, p < 0.001). IL‐6 values in plasma and cultures were found independently associated with PFH of premature CAD (p < 0.001, p = 0.005, respectively). A similar relation was found for TNF‐a values measured in cultures (p = 0.005) and CRP values in plasma (p < 0.001). The values of IL‐6 were found proportionally related to TG.
Conclusion
In individuals with PFH of CAD the inflammatory process of atheromatosis appears to begin early in childhood. Except for triglycerides, this inflammatory process appears to occur independently of several traditional cardiovascular risk factors. Copyright © 2010 Wiley Periodicals, Inc.
Keywords: Atherosclerosis in children, pro‐iflammatory cytokines in children, IL‐6, TNF‐a, family history of cardiovascular disease and atherosclerosis, monocytes cultures
Full Text
The Full Text of this article is available as a PDF (205.0 KB).
References
- 1. Davies H: Atherogenesis and the coronary arteries of childhood. Int J Cardiol 1990; 28: 283–291. [DOI] [PubMed] [Google Scholar]
- 2. Napoli C, D'Armiento FP, Mancini FP, Postiglione A, Witztum JL, et al.: Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia, intima accumulation of low density lipoproteins and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997; 100(11): 2680–2690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Kaprio J, Norio R, Personen E, Sarna S: Intimal thickening of the coronary arteries in infants in relation to family history of coronary artery disease. Circulation 1993; 87: 1960–1968. [DOI] [PubMed] [Google Scholar]
- 4. Myers RH, Kiely DK, Cupples LA, Kannel WB: Parental history is an independent risk factor for coronary artery disease: The Framingham Study. Am Heart J 1990; 120: 963–969. [DOI] [PubMed] [Google Scholar]
- 5. Jousilathi P, Puska P, Vartiainen E, Pekkanen J, Tuomilehto J: Parental history of premature coronary artery disease: An independent risk factor of myocardial infarction. J Clin Epidemiol 1996; 49: 497–503. [DOI] [PubMed] [Google Scholar]
- 6. Berenson GS, Wattigney WA, Tracy RE, Newman WP, Srinivasan SR, et al.: Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (the Bogalusa Heart Study). Am J Cardiol 1992; 70: 851–858. [DOI] [PubMed] [Google Scholar]
- 7. Stary HC: The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life. Eur Heart J 1990; II:Suppl E: 3–19. [DOI] [PubMed] [Google Scholar]
- 8. Galis Z, Sukhova G, Kranzhofer R, Clark S, Libby P. Macrophage foam cells from experimental atheroma constitutively produce matrix degrading proteinases. Proc Natl Acad Sci USA 1995; 92(2): 402–406. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. National high blood pressure education program working group on hypertension control in children and adolescents. Pediatrics 1996; 98: 649–658. [PubMed] [Google Scholar]
- 10. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low‐density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502. [PubMed] [Google Scholar]
- 11. Ohta T, Saku K, Takata K, Adachi N: Soluble vascular cell‐adhesion molecule‐1 and soluble intercellular adhesion molecule 1 correlate with lipid and apolipoprotein risk factors for coronary artery disease in children. Eur J Pediatr 1999; 158(7): 592–598. [DOI] [PubMed] [Google Scholar]
- 12. Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002; 105: 1135–1143. [DOI] [PubMed] [Google Scholar]
- 13. Smitko PE, Wang C‐H, Weisel RD, Jeffries GA, Anderson TJ, et al.: New markers of inflammation and endothelial cell activity. Circulation 2003; 108: 1917–1923. [DOI] [PubMed] [Google Scholar]
- 14. Schindler R, Mancilla J, Endres S, Ghorbani R, Clark SC, et al.: Correlations and interactions in the production of interleukin‐6 [IL‐6], IL‐1,and tumor necrosis factor [TNF] in human blood mononuclear cells: IL‐6 suppresses IL‐1 and TNF. Blood 1990; 75(1): 40–47. [PubMed] [Google Scholar]
- 15. Gaeta G, De Michele M, Cuomo S, Guarinini P, Foglia M, et al.: Arterial abnormalities in the offspring of patients with premature myocardial infarction. N Engl J Med 2000; 343(12): 840–846. [DOI] [PubMed] [Google Scholar]
- 16. de Jongh S, Lilien MR, Bakker HD, Hutten BA, Kastelein JJ, et al.: Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis 2002; 163: 193–197. [DOI] [PubMed] [Google Scholar]
- 17. Barth JA, Deckelbaum RJ, Starc TJ, Shea S, Mosca L, et al.: Family history of early cardiovascular disease in children with moderate to severe hypercholesterolemia: Relationship to lipoprotein [a] and low‐density lipoprotein cholesterol levels. J Lab Clin Med 1999; 133: 237–244. [DOI] [PubMed] [Google Scholar]
- 18. Pasceri V, Wilerson JT, Yeh ET: Direct proinflamatory effect of C‐reactive protein on human enthothelian cells. Circulation 2000; 102: 2165–2168. [DOI] [PubMed] [Google Scholar]
- 19. Lefkou E, Fragakis N, Varlamis G: The inflammatory process during childhood and the risk of developing atheromatous disease in adult life: the role of C‐reactive protein. Hellenic J Cardiol 2006; 47(2): 89–94. [PubMed] [Google Scholar]
- 20. Ridker PM: High‐sensitivity C‐reactive protein; Potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001; 103: 1813–1818. [DOI] [PubMed] [Google Scholar]
- 21. Haddy N, Sass C, Droesch S, Zaiou M, Siest G, et al.; IL‐6, TNF‐a and atherosclerosis risk in a healthy family population: The STANISLAS cohort. Atherosclerosis 2003; 170(2): 277–283. [DOI] [PubMed] [Google Scholar]
- 22. Zeltser D, Rogowski O, Fusman R, Rotstein R, Rubinstein A, et al.: The multiplicity of atherosclerotic risk factors corresponds to the appearance of increased leukocyte count in the peripheral blood: Relevance to the pathogenesis of the disease. J Cardiovasc Risk 2001; 8: 379–388. [DOI] [PubMed] [Google Scholar]
- 23. Choi YH, Lee W, Lee Y, Kim JK, Lee SY, et al.: Correlation between monocyte and T‐lymphocyte activation markers in patients with acute coronary syndrome. Jpn Heart J 2000; 41(5): 605–615. [DOI] [PubMed] [Google Scholar]
- 24. Bao W, Srinivasan SR, Wattigney WA, Berenson GS: The relation of parental cardiovascular disease to risk factors in children and young adults. The Bogalusa Heart Study. Circulation 1995; 91: 365–371. [DOI] [PubMed] [Google Scholar]
- 25. Biegel Y, George J, Lcibovici I, Mattityahu A, Sclaroversusky S, et al.: Coronary risk factors in children of parents with premature coronary artery disease. Acta Paediatr 1993; 82(2): 162–165. [DOI] [PubMed] [Google Scholar]
- 26. Bao W, Srinivasan SR, Valdez R, Greenlund KJ, Wattigney WA, et al.: Longitudinal changes in cardiovascular risk from childhood to young adulthood in offspring of parents with coronary artery disease. The Bogalusa Heart Study. JAMA 1997; 278(21): 1749–1754. [PubMed] [Google Scholar]
- 27. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH: Plasma concentration of interleukin‐6 and the risk of future myocardial infarction among healthy men. Circulation 2000; 101: 1767–1772. [DOI] [PubMed] [Google Scholar]
- 28. Bermudez EA, Rifai N, Buring J, Manson JE, Ridker PM: Interrelationships among circulating interleukin‐6, C‐reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 2002; 22(10): 1668–1673. [DOI] [PubMed] [Google Scholar]
- 29. Badenhop RF, Wang XL, Wiken DEL: Angiotensin converting enzyme genotype in children and coronary artery events in their grandparents. Circulation 1995; 91: 1655–1658. [DOI] [PubMed] [Google Scholar]
- 30. Thompson SR, Novick D, Stock CJ, Sanders J, Brull D, et al.: Free interleukin (IL)‐18 levels, and the impact of IL18 and IL18BP genetic variation, in CHD patients and healthy men. Arterioscler Thromb Vasc Biol 2007; 27: 2743–2749. [DOI] [PubMed] [Google Scholar]
